Certain embodiments are directed to the fields of chemistry and medicine. Certain aspects are directed to compounds for treating chronic pancreatitis, colon cancer, or liver fibrosis.
Chronic pancreatitis (CP) is a progressive, non-curable disorder of the pancreas (Schneider and Whitcomb, 2002, Best Pract Res Clin Gastroenterol 16:347). Pathologically, both the endocrine and exocrine pancreas undergo progressive and often irreversible morphological changes, including glandular fibrosis (Bordalo et al. 1977, Am J Gastroenterol 68:278; Shimizu 2008, Gastroenterol 43:823; Sahel and Sarles 1979, Dig Dis Sci 24:897; Witt et al. 2007, Gastroenterology 132:15570). In the United States, disorders of the exocrine pancreas affect over 1 million patients and result in a cost of over $3.7 billion annually (Yang et al. 2008, Arch Intern Med 168:649; Everhart and Ruhl 2009, Gastroenterology 136:376). Current treatment options for CP are limited to supportive and palliative care; patients with advanced disease can be managed with endoscopic and/or surgical pancreatic decompression, denervation, resection, bypass, or transplantation (Trikudanathan et al. 2012, Gastroenterol Clin North Am 41:63; Forsmark 2013, Gastroenterology 144:1282). Overall, patients have a poor quality of life, and are burdened by chronic abdominal pain, increased hospitalizations, impaired digestion, diarrhea, weight loss, diabetes, complications like pseudocysts and an increased risk of pancreatic cancer (Forsmark 2013, Gastroenterology 144:1282). Therefore, the development of effective, safe and affordable therapeutic agents remains a critical need.